Technical Abstract:
Curcumin has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic, curcumin has a broad range of beneficial properties to human health. Recently, active research on curcumin with respect to aging and related traits in model organisms has demonstrated that curcumin and its metabolite, tetrahydrocurcumin (THC), increase mean lifespan of at least three model organisms: nematode roundworm, fruit fly Drosophila, and mouse. Nematodes grown on media containing curcumin showed a significantly increased lifespan by reducing the production of reactive oxygen species (ROS). Genes osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1, and age-1 are required for curcumin-mediated lifespan extension. The lifespan extension of Drosophila by curcumin supplementation was associated with increased superoxide dismutase (SOD) activity, and decreased lipofuscin, malondialdehyde (MDA) levels. Curcumin up-regulated expressions of SOD genes, and down-regulated expressions of several age-related genes, such as dInR, ATTD, Def, CecB, and DptB. In addition, THC extended lifespan in Drosophila and inhibited oxidative stress response by regulating FOXO and Sir2. Mice fed diets containing THC starting at the age of 13 months had significantly increased mean lifespan. In summary, the positive effects of curcumin on lifespan extension likely arise from beneficial regulation of oxidative stress responses and age-related genes. Understanding the molecular mechanism(s) of curcumin action has provided base knowledge and rationale for future human clinical trials, and for nutritional intervention in aging and age-associated disorders in humans.